Interactions of Co(II)- and Zn(II)porphyrin of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin with DNA in Aqueous Solution and Their Antimicrobial Activities.

Antibiotics are frequently used to treat, prevent, or control bacterial infections, but in recent years, infections resistant to all known classes of conventional antibiotics have significantly grown. The development of novel, nontoxic, and nonincursive antimicrobial methods that work more quickly and efficiently than the present antibiotics is required to combat this growing public health issue. Here, Co(II) and Zn(II) derivatives of tetrakis(1-methylpyridinium-4yl)porphyrin [H2TMPyP]4+ as a tetra(ρ-toluenesulfonate) were synthesized and purified to investigate their interactions with DNA (pH 7.40, 25 °C) using UV-vis, fluorescence techniques, and antimicrobial activity. UV-vis results showed that [H2TMPyP]4+ had a high hypochromicity (∼64%) and a substantial bathochromic shift (Δλ, 14 nm), while [Co(II)TMPyP]4+ and [Zn(II)TMPyP]4+ showed little hypochromicity (∼37%) and a small bathochromic shift (Δλ, 3-6 nm). Results reveal that [H2TMPyP]4+ interacts with DNA via intercalation, while Co(II)- and [Zn(II)TMPyP]4+ interact with DNA via outside self-stacking. Fluorescence results also confirmed the interaction of [H2TMPyP]4+ and the metalloporphyrins with DNA. Results of the antimicrobial activity assay revealed that the metalloporphyrins showed inhibitory effects on Gram-positive and Gram-negative bacteria and fungi, but that neither the counterions nor [H2TMPyP]4+ exhibited any inhibitory effects. Mechanism of antimicrobial activities of metalloporphyrins are discussed.

Interactions of linagliptin, rabeprazole sodium, and their formed complex with bovine serum albumin: Computational docking and fluorescence spectroscopic methods.

The foremost aim of this thermodynamic study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of linagliptin (LG), rabeprazole sodium (RS), and their 1:1 formed complex by interacting with bovine serum albumin (BSA) at physiological pH 7.4. The molecular interactions of these ligands with the desired biomolecule were substantiated by the spectral quelling of fluorescence intensity of BSA. The fluorescent test and molecular docking revealed that the quenching mechanism was a spontaneous and exothermic static process, and the protein gained its secondary structure due to the interactions. The spectroscopic method was exercised to determine the thermodynamic factors that supported the interactions mediated by van der Waals forces and hydrogen bonds. The activation energy of the formed complex was higher than its precursor drugs while interacting with BSA, and the energy transformation profiles were studied by UV-fluorescence overlaid curves according to Förster resonance energy transfer (FRET) theory. The double log plot verified that these ligands bound with protein at a 1:1 ratio, which was confirmed by the approximately estimated values of the binding parameters. The drastically lower value of the binding constant of the formed complex suggested the lower half-life as well as its triggered elimination rate from the cardiovascular system, which may be an initial indicator of the reduced hypoglycemic property of linagliptin. Moreover, the UV-vis and synchronous fluorescence spectroscopic methods affirmed the conformational changes of the BSA due to drug-protein complexation and polarity alterations in the microenvironment of disparate chromophores of the biomolecule.

Transition Metal Chelation Augments the Half-life of Secnidazole: Molecular Docking and Fluorescence Spectroscopic Approaches.

This current research aimed to establish the most required pharmacodynamics parameters of two transition metal complexes of an antimicrobial drug secnidazole. The spectroscopic fluorescence quenching strategy was outlined to evaluate the binding mechanism and binding affinity of nickel (II) and chromium (III) complexes of secnidazole with bovine serum albumin (BSA). The conformational modifications and the interacting patterns of the protein due to the interaction of the parent compound of the metal complexes have been investigated by molecular docking approach. The ligand-protein interactions were confirmed by the spectral quelling of the serum protein's intensity in the presence of metal chelate of secnidazole. The quenching mechanism was an endothermic dynamic process. The calculated thermodynamic factors delineated van der Waals interactions mainly influenced the spontaneous process. The UV-fluorescence curves were studied to establish the energy transformation profile according to the Förster resonance energy transfer (FRET) theory. The double-logarithm plot exhibited the binding number that ensured the drug-protein interaction was at a 1:1 ratio. The compared binding constants dictated that both metal chelates gained higher binding affinity, longer half-life, and achieved the capacity to show the pharmacological effects by a lower dose than the parent molecule.

Does Rabeprazole Sodium Alleviate the Anti-diabetic Activity of Linagliptin? Drug-Drug Interaction Analysis by In vitro and In vivo Methods.

Drug interaction has turned into the preeminent regarding issues for a prescriber during polypharmacy. The foremost objective of this research was to form a complex between linagliptin and rabeprazole sodium by in vitro interactions. The interactions between the drugs have been examined by monitoring some chromatographic and spectroscopic analyses viz. TLC, HPLC, FT-IR, UV, Job's plot, conductometric titrations, and Ardon's spectrophotometric strategy. Rabeprazole sodium formed a stable complex with linagliptin, which was ensured from the insight of these analytical data. The developed complex's bright spot was clearly watched in the TLC plate. The retention time (Rt) of the formed complex was 5.303 min, where the Rt were 3.364 and 3.103 min for linagliptin and rabeprazole sodium, respectively, in HPLC chromatograms. In FT-IR and UV spectra of the formed complex revealed some disappearance of characteristic peaks that affirmed the complexation. All of the variations of the spectrophotometric and chromatographic properties from the antecedent drugs indicated the drug-drug interaction. Another crucial fact for the experimental aim was to affirm the assumed drug interaction by in vivo model examination. The assessment of anti-diabetic property on alloxan-induced Swiss albino mice proved significant in vivo interaction between the drugs. It was outlined from the animal study that the hypoglycemic activity of linagliptin might be significantly affected due to the complex formation of the drug with a proton pump inhibitor (PPI). Nonetheless, it is the primary outcome of the interaction, which recommends the bigger in vivo study or clinical monitoring on the human model.

Analysis of aceclofenac and bovine serum albumin interaction using fluorescence quenching method for predictive, preventive, and personalized medicine.

BACKGROUND: The study of the interaction of a drug with plasma protein is very important because drug-protein binding plays an important role in determination of pharmacological and toxicological properties of drugs. Our study was designed to investigate the interaction between aceclofenac and bovine serum albumin (BSA) using fluorescence spectroscopy at different temperatures (298 and 308 K). METHODS: Fluorescence spectroscopy was used to carry out the study. Fluorescence quenching constant was determined from Stern-Volmer equation. Van't Hoff equation was used to determine the thermodynamic parameters such as free energy (ΔG), enthalpy (ΔH), and entropy (ΔS). RESULTS: The experimental data showed that the quenching of BSA by aceclofenac was due to a formation of a BSA-aceclofenac complex with probable involvement of both tryptophan and tyrosine residues of BSA. Dynamic quenching was shown for BSA by aceclofenac at the experimental conditions. The values of thermodynamic parameters indicated that the hydrophobic forces played major roles for BSA-aceclofenac complexation. The binding number (n) was found to be ≈1 indicating that 1 mol of BSA bound with 1 mol of aceclofenac. The binding affinity of aceclofenac to BSA was calculated at different temperatures. It was shown that the binding constant decreased with increasing temperatures indicating that stability of the BSA-aceclofenac complex decreased with increasing temperatures. CONCLUSIONS: The interaction of aceclofenac with BSA was successfully explored using a fluorescence spectroscopic technique.

A novel ion-pair RP-HPLC method for simultaneous quantification of naproxen and esomeprazole in pharmaceutical formulations.

A rapid, sensitive and stability indicating ion-pair reversed-phase high-performance liquid chromatographic method was developed for simultaneous estimation of naproxen (NPX) and esomeprazole (ESP) in pharmaceutical preparations. In our study, this new method was used to overcome the instability problem of ESP during high-performance liquid chromatographic analysis in the presence of acidic drugs such as NPX. The method was validated according to ICH, FDA and USP guidelines with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity and system suitability. The method was developed by using an isocratic condition of mobile phase comprising buffer [tetrabutylammonium hydroxide (0.0077 M) and n-heptane sulfonic acid-Na salt (0.002 M), pH 7.6], acetonitrile and methanol in a 60 : 20 : 20 v/v/v ratio at a flow rate of 1.5 mL/min over a C-18 (Octadecyl-silica, 5 µm, 250 × 4.6 mm) column at ambient temperature. The recovery for both drugs was found to be >99% which demonstrated the accuracy of this method. Intra- and inter-day precision studies of the new method were less than the maximum allowable limit [% relative standard deviation (RSD) ≤2.0 according to FDA]. The method showed linear response with a correlation coefficient (r(2)) value of 0.999 for both drugs. More importantly, ESP was quite stable in diluting solvent and mobile phase in the presence of NPX for >3 days. Therefore, it was found to be an accurate, reproducible, sensitive and highly stability-indicating method and can be successfully applied for routine analysis of simultaneous assay of NPX and ESP in pharmaceutical dosage forms.

Anti-acne activities of pulsaquinone, hydropulsaquinone, and structurally related 1, 4-quinone derivatives.

Quinone type compound, pulsaquinone 1, isolated from the aqueous ethanol extract of the roots of Pulsatilla koreana exhibited antimicrobial activities against an anaerobic non-spore-forming gram-positive bacillus, Propionibacterium acnes, which is related with the pathogenesis of the inflamed lesions in a common skin disease, acne vulgaris. Compound 1 was unstable on standing and thus converted to more stable compound 2, namely hydropulsaquinone by hydrogenation, whose activity was comparable to mother compound 1 (MIC for 1 and 2 against P. acnes: 2.0 and 4.0 microg/mL, respectively). Other structurally-related quinone derivatives (3-13) were also tested for structure-activity relationship against anaerobic and aerobic bacteria, and fungi. The antimicrobial activity was fairly good when the quinone moiety was fused with a nonpolar 6- or 7-membered ring on the right side whether or not conjugated (1,4-naphtoquinone derivatives 3-5), while simple quinone compounds 6-9 showed poor activity. It seems that the methoxy groups at the left side of the quinone function deliver no considerable antimicrobial effect.

Labdane-type diterpenes active against acne from pine cones (Pinus densiflora).

Bioassay-guided extraction and fractionation of the aqueous methanolic extract of the cones of Pinus densiflora (Pinaceae) afforded one new labdane-type diterpene aldehyde, 15-nor-14-oxolabda-8(17),12 E-diene-18-oic acid, along with eight known diterpenes. Their structures were elucidated using spectroscopic methods as well as by comparison with previously reported data. The isolates showed antibacterial (Propionibacterium acnes) and antifungal activities.